Neurodevelopmental actions of leptin

Abstract

Leptin is well known as an important hormone in the central control of feeding behavior. During development, fetuses and newborns are exposed to leptin and recent evidence has shown that leptin receptors are widespread throughout the developing brain. Accordingly, leptin affects brain development during both pre- and postnatal life. The actions of leptin in the developing brain are generally permanent and range from the establishment of hypothalamic circuits to plasticity in cortical pathways. The cellular events mediated by leptin include the following: neurogenesis, axon growth, and synaptogenesis. Nutritional manipulation of leptin secretion during perinatal life has generated considerable concern, and the developing brain appears to be a particularly sensitive target for these environmental changes.

Figure 1. Leptin targets in the developing brain

Schematic drawing (horizontal section) of the distribution of leptin receptor-containing neurons in the postnatal and adult mouse brains. The staining found in the adult PMV was taken as a reference signal for the highest score, and the staining in the postnatal LHA was taken as a reference signal for the lowest score. Adapted from [13], with permission.

Figure 2. Developmental actions of leptin in the forebrain

Schematic illustration representing the neurodevelopmental effects of leptin. During pre- and postnatal life, leptin appears to be required for the normal development of forebrain pathways by regulating neurogenesis and circuit formation. In addition, leptin can still affect brain plasticity in adults by causing synaptic rearrangement of excitatory and inhibitory inputs on hypothalamic neurons and by influencing cell proliferation in the hippocampus. Images used with permission [10,46,55]